Low-incidence Countries Research Articles

Tuberculosis in migrants to Australia: Outcomes of a national screening program

Background: Few low-incidence countries are on track to achieve the ambitious target of reaching TB pre-elimination by 2035. Australia is a high-income country with a low burden of TB, which is particularly concentrated in migrant populations. As part of Australia's migration program, permanent, provisional and humanitarian visa applicants are screened for TB, along with some applicants for temporary visas.Methods: We calculated the prevalence of all forms of active TB and bacteriologically-confirmed TB among onshore and offshore applicants for visas to Australia from July 2014 to June 2017, and investigated associated risk factors using logistic regression.Findings: Visa applicants were predominantly young adults from various Asian countries. Among 2,381,217 applicants, 1263 cases of active TB were diagnosed, including 852 cases of bacteriologically-confirmed TB. Overall TB prevalence was 53.0 per 100,000, corresponding to one TB diagnosis for every 1887 applicants screened. TB rates increased with age and were higher among humanitarian applicants and those previously treated for TB, although most cases occurred in applicants without these risk factors. TB prevalence by country of origin was similar to WHO estimates for some countries, but considerably lower for others. For several highly represented countries of origin, rates appear to have fallen relative to earlier comparable studies.Interpretation: Prevalence of TB among visa applicants to Australia and the consequent risk to the Australian community appear to be declining and remain low. In this context, support for TB control programs overseas and preventive interventions are likely to have the greatest impact on domestic TB burden.Funding: No specific funding was received for this study. JMT is a recipient of an Early Career Fellowship from the Australian National Health and Medical Research Council (APP1142638).

Specific Host Signatures for the Detection of Tuberculosis Infection in Children in a Low TB Incidence Country.

Diagnosis of tuberculosis (TB) in children remains challenging due to unspecific clinical presentation and low bacillary load. In low TB incidence countries, most cases are diagnosed by a contact screening strategy after exposure to an index TB case. Due to the severity of TB in young children, the priority is to determine whether a child is infected or not, whereas differential diagnosis between active TB (aTB) and latent TB constitutes a second step. In Belgium, a low TB incidence country, we prospectively included 47 children with a defined M. tuberculosis infection status (12 children with aTB, 18 with latent TB, and 17 uninfected) (exploratory cohort), and determined the optimal combinations of cytokines secreted by their peripheral blood mononuclear cells in response to a 5-days in vitro stimulation with four different mycobacterial antigens, in an attempt to classify the children according to their infectious status. Correct identification of all infected children was obtained by several combinations of two purified protein derivative (PPD)-induced cytokines (IFN-γ and either GM-CSF, MIP-1α, sCD40L or TNF-α), or by combining PPD-induced IFN-γ with culture-filtrate protein-10 (CFP-10)-induced TNF-α. Alternatively, combining CFP-10-induced TNF-α and IP-10 with heparin-binding haemagglutinin (HBHA)-induced-IFN-γ was more effective in testing recently BCG-vaccinated children or those suspected to be infected with non-tuberculous mycobacteria, providing a correct classification of 97% of the M. tuberculosis-infected children. This combination also correctly classified 98% of the children from a validation cohort comprising 40 M. tuberculosis infected children and 20 non-infected children. Further differentiation between aTB and children with latent TB was more difficult. Combining ESAT-6-induced MIP1-α and IP-10, CFP-10-induced MIG, and HBHA-induced MIG provided a correct classification of 77% of the children from the exploratory cohort but only of 57.5% of those from the validation cohort. We conclude that combining the measurement of 2–4 cytokines induced by three different mycobacterial antigens allows an excellent identification of M. tuberculosis-infected children, whereas differentiating children with aTB from those with latent TB remains far from perfect.

Needle in a haystack: Looking for tuberculosis in a low-incidence setting.

Canada is a low-incidence country for tuberculosis (TB). The BC Public Health Laboratory diagnostic algorithm for pulmonary TB includes acid fast bacilli (AFB) smear and mycobacterial culture of all submitted sputa. TB nucleic acid amplification testing (NAT) is routinely performed on AFB-smear-positive (AFB+) sputa only. We assessed the laboratory-associated costs of implementing the international recommendations for TB NAT on AFB-smear-negative (AFB-) sputa. Two data sets were obtained: (1) all AFB- samples for a 3-year period (October 1, 2014-September 30, 2017) and (2) all AFB-, TB-culture-positive samples for the same period. One AFB- sample/patient from each defined diagnostic set of sputa was deemed eligible for TB NAT. To stratify patients by ordering location, a 1-year subset of data (October 1, 2016-September 30, 2017) was examined. In the 3-year period, 0.7% of all diagnostic sets were AFB- and culture-positive. In the 1-year period, the provincial TB Services clinics submitted 26% of all AFB- samples received, but these constituted 78% of AFB-, culture-positive samples. The annual cost of TB NAT on one AFB- sputum sample from each eligible diagnostic set would total approximately $247,000. Targeting only TB Services clinic patients would reduce this cost to approximately $64,000/year while capturing more than 75% of AFB-, culture-positive patients. On the basis of our provincial positivity rate, it would cost approximately $6,000 to provide an early TB diagnosis for an AFB-, culture-positive patient. The cost-effectiveness to public health of this approach in a TB low-incidence setting needs to be carefully evaluated.

Geographical Distribution of E-cadherin Germline Mutations in the Context of Diffuse Gastric Cancer: A Systematic Review.

Simple SummaryE-cadherin (CDH1 gene) germline mutations are associated with the development of the autosomal cancer syndrome known as hereditary diffuse gastric cancer. About 30% of families fulfilling the clinical criteria established by the International Gastric Cancer Linkage Consortium have constitutional alterations of the CDH1 gene. Different patterns of CDH1 germline mutations have described as truncating, deletion, insertion, splice site, non sense, silence, and at last, missense alterations. The frequency of the different E-cadherin germline mutations in countries with different incidence rates for gastric carcinoma has reported extremely variable. In this study we aimed to assess the worldwide frequency of CDH1 germline mutations in gastric cancers coming from different geographical areas, using a systematic approach.Hereditary diffuse gastric cancer (HDGC) is a complex and multifactorial inherited cancer predisposition syndrome caused by CDH1 germline mutations. Nevertheless, current CDH1 genetic screening recommendations disregard an unbalanced worldwide distribution of CDH1 variants, impacting testing efficacy and patient management. In this systematic review, we collected and analyzed all studies describing CDH1 variants in gastric cancer patients originating from both high- and low-prevalence countries. Selected studies were categorized as family study, series study, and unknown study, according to the implementation of HDGC clinical criteria for genetic testing. Our results indicate that CDH1 mutations are more frequently identified in gastric cancer low-incidence countries, and in the family study group that encompasses cases fulfilling criteria. Considering the type of CDH1 alterations, we verified that the relative frequency of mutation types varies within study groups and geographical areas. In the series study, the missense variant frequency is higher in high-incidence areas of gastric cancer, when compared with non-missense mutations. However, application of variant scoring for putative relevance led to a strong reduction of CDH1 variants conferring increased risk of gastric cancer. Herein, we demonstrate that criteria for CDH1 genetic screening are critical for identification of individuals carrying mutations with clinical significance. Further, we propose that future guidelines for testing should consider GC incidence across geographical regions for improved surveillance programs and early diagnosis of disease.

Tackling TB in migrants arriving at Europe’s southern border

Over a quarter of the individuals diagnosed with tuberculosis [TB] in the European Union region are born outside of the area and the proportion has been increasing steadily. Italy is a low TB incidence country with over 50% of TB cases in the foreign-born population primarily due to the high numbers of migrants entering the country via land or sea. As a case study to evaluate the value of screening in newly arrived migrants, the EDETECT-TB project in Italy implemented and evaluated active TB screening in the migrant population at first reception centres to ensure early diagnosis to avoid further spread. Based on a cost-effectiveness analysis from a program provider perspective, a decision tree model allowed the assessment of the value for money of case finding by estimating the cost per case of active TB detected compared with the status quo of no screening. The analysis confirmed that early case detection is a cost-effective intervention in areas with migrants arriving from high TB risk settings. Targeted post-arrival early screening of high TB risk vulnerable new entrants to Italy has a potential role in reducing the spread of TB among migrants.

Tracking the Origin of Austrian Human Brucellosis Cases Using Whole Genome Sequencing.

Brucellosis is a zoonotic disease caused by Brucella spp. and a major concern for livestock. Most human cases are caused by B. melitensis and clinical presentation is usually a mild febrile illness. However, treatment failure is frequent and more severe complications can occur. In Austria, every human brucellosis is investigated to determine whether it was imported from endemic areas or is the sign of an undetected autochthonous transmission. For this study, 21 B. melitensis strains isolated in Austria between 2005 and 2019 were collected, 17 strains from 15 different patients and four strains from cattle. Whole genome sequencing combined with core-genome MLST analysis was used to characterize these strains. A cluster of seven isolates from 2018 (three human and four cattle isolates) was identified, with fewer than two allelic differences. They corresponded to the only Austrian B. melitensis outbreak that happened over the past 15 years. The other 12 Austrian brucellosis cases were single cases, and geographical origins were available for 8/12. Genomic data was used to locate probable geographical origins and compared with the results of the epidemiological investigations. Austrian strains were compared with 67 published B. melitensis sequences available on NCBI. The result of genomic analysis matched for 7/8 cases with documented conclusion of the epidemiological investigation. Genome analysis also pointed to the geographical origin for three of the four cases with missing epidemiological data. Strains from six cases were grouped together (<40 allelic differences) with 4/6 cases imported from the Balkans. Additional B. melitensis isolates from Serbian animals were analyzed and grouped with this branch, suggesting frequent importation from Balkan countries to Austria. Overall, this study highlights the specificities of human brucellosis in Austria. It also underlines the value of whole genome sequencing as a tool to investigate brucellosis cases, allowing to identify and investigate outbreaks but also to support epidemiological investigation of imported cases. However, the reliability of such methods depends on the number of strains for comparison, which can be challenging in low incidence countries. Increasing the availability of published sequences with documented geographical origins would help establishing genomic-based methods for investigating brucellosis cases.

Effects of migration on tuberculosis epidemiological indicators in low and medium tuberculosis incidence countries: A systematic review

BackgroundTuberculosis (TB) remains one of the top ten causes of death each year globally. While the risk of migrant TB is linked to the TB incidence in their country of origin, the migration process can increase the TB risk. ObjectiveWe aimed to synthesis the evidence on key differences in the epidemiological profile of TB between migrants from high TB incidence birth countries and non-migrants resident in low to medium incidence TB countries. MethodsWe conducted a systematic review where the population was all active TB cases in countries with low to medium TB incidence (<40/100,000 population), the exposure was migration to a low or medium TB incidence country and the comparator was non-migrant TB cases in low or medium incidence countries. Overall proportions were compared between migrants and non-migrants, using Fisher’s exact test. Meta-analysis of proportions was carried out for the primary outcome (active TB) while meta-analyses of odds ratios (ORs) were performed using a random effects model for secondary outcomes; sputum-smear positivity, any first line drug resistance, multi-drug resistance (MDR), clustered cases, HIV coinfections and successful treatment. Heterogeneity was evaluated and sources were investigated using subgroup and sensitivity analysis. ResultsSignificant differences were found in the overall proportions of high TB incidence migrants and non-migrants for MDR cases, clustered cases, HIV coinfections and successful treatment, as well as a significant difference in the OR among MDR cases (3.91). ConclusionThis review has demonstrated significant differences in key epidemiological indicators between high TB incidence migrants and non-migrants, indicating policy implications.

Factors associated with the progression of gastric intestinal metaplasia: a multicenter, prospective cohort study.

Background and study aims Gastric cancer (GC) is usually preceded by premalignant gastric lesions (GPLs) such as gastric intestinal metaplasia (GIM). Information on risk factors associated with neoplastic progression of GIM are scarce. This study aimed to identify predictors for progression of GIM in areas with low GC incidence. Patients and methods The Progression and Regression of Precancerous Gastric Lesions (PROREGAL) study includes patients with GPL. Patients underwent at least two upper endoscopies with random biopsy sampling. Progression of GIM means an increase in severity according to OLGIM (operative link on gastric intestinal metaplasia) during follow-up (FU). Family history and lifestyle factors were determined through questionnaires. Serum Helicobacter pylori infection, pepsinogens (PG), gastrin-17 and GC-associated single nucleotide polymorphisms (SNPs) were determined. Cox regression was performed for risk analysis and a chi-squared test for analysis of single nucleotide polymorphisms. Results Three hundred and eight patients (median age at inclusion 61 years, interquartile range (IQR: 17; male 48.4 %; median FU 48 months, IQR: 24) were included. During FU, 116 patients (37.7 %) showed progression of IM and six patients (1.9 %) developed high-grade dysplasia or GC. The minor allele (C) on TLR4 (rs11536889) was inversely associated with progression of GIM (OR 0.6; 95 %CI 0.4–1.0). Family history (HR 1.5; 95 %CI 0.9–2.4) and smoking (HR 1.6; 95 %CI 0.9–2.7) showed trends towards progression of GIM. Alcohol use, body mass index, history of H. pylori infection, and serological markers were not associated with progression. Conclusions Family history and smoking appear to be related to an increased risk of GIM progression in low GC incidence countries. TLR4 (rs11536889) showed a significant inverse association, suggesting that genetic information may play a role in GIM progression.

International cost-effectiveness analysis evaluating endoscopic screening for gastric cancer for populations with low and high risk

Gastric cancer remains one of the 3 most common causes of cancer death worldwide. Understanding the health and economic factors that affect screening cost-effectiveness in different countries will help address when and where it makes most sense to screen for gastric cancer. We performed a cost-effectiveness analysis using a Markov model to compare screening and surveillance strategies for gastric cancer in Brazil, France, Japan, Nigeria, and the United States. Primary outcome was the incremental cost-effectiveness ratio. We then performed a sensitivity analysis to determine how each variable affected the overall model. In all countries, the most cost-effective strategies, measured by incremental cost-effectiveness ratio relative to no screening, were screening every 10years, surveillance of high- and low-risk patients every 5 and 10 years, respectively, and screening every 5years. Only Japan had at least one cost-effective screening strategy. The most important variables across different screening strategies and countries were starting age of screening, cost of endoscopy, and baseline probability of local gastric cancer at time of diagnosis. Our model suggests that screening for gastric cancer is cost-effective in countries with higher incidence and lower costs of screening, but screening may still be a viable option in high-risk populations within low incidence countries.

Chronic pulmonary aspergillosis: prevalence, favouring pulmonary diseases and prognosis.

Chronic pulmonary aspergillosis (CPA) is an emerging disease in patients with common chronic pulmonary diseases (CPDs). While its prevalence is linked to tuberculosis (TB) in endemic countries, epidemiological and prognostic data are lacking in low TB incidence countries. The aim of this study was to describe these features in CPA patients hospitalised in France between 2009 and 2018.We estimated the prevalence and mortality of hospitalised CPA patients using the French nationwide administrative hospital database. We also assessed the association with CPD, thoracic interventions and malnutrition.From 2009 to 2018, 17 290 patients were hospitalised in France for CPA, with an increasing prevalence during this period. Most patients were male (63.5%) with a median age of 65 years at CPA diagnosis, living in farming regions and large cities. The proportion of underlying chronic obstructive pulmonary disease (COPD) and emphysema during the previous 5 years was 44% and 22%, respectively, whereas it was only 3% for both TB and non-TB mycobacterial (NTM) infections. The mortality rates during the first hospitalisation, at 1 year and at 5 years were 17%, 32% and 45%, respectively. In multivariate analysis, mortality rates were increased in patients aged >65 years, male patients and patients with malnutrition, diabetes or lung cancer history. The risk of mortality in patients with COPD or emphysema was higher than in those with previous mycobacterial lung infection.In France, CPA is an emerging infection commonly associated with non-mycobacterial CPD. This shift in the distribution profile of underlying CPD will likely worsen CPA mortality.

Tuberculosis in Children Hospitalized in a Low-burden Country: Description and Risk Factors of Severe Disease.

In high-income countries, few pediatric studies have described the clinical expression of tuberculosis (TB) according to age, and their results are discordant. Patients <2 years of age are usually considered to be at higher risk for severe disease than older children. Our aim was to better describe pediatric TB disease severity in a low-incidence country. All children (<18 years of age) admitted with TB disease to the Robert Debré University Hospital, Paris, between 1992 and 2015 were included. Patients were classified by the severity of TB disease based on the original classification of Wiseman et al. Risk factors associated with severity were analyzed. We included 304 patients with a median age of 9.9 years (interquartile range 3.3-13.3) and a male to female ratio of 1.04. Overall, 280/304 (92%) were classified: 168/304 (55%) were classified as showing severe TB and 112/304 (37%) as showing non-severe TB. Central nervous system disease was more frequent among patients <2 years of age than patients 2-17 years of age (5/54; 9% vs. 5/229; 2% P = 0.024). An age of ≥10 years (P = 0.001) and being born abroad (P = 0.011) were both associated with disease severity in univariate analysis. In multivariate analysis, diagnosis through symptom-based screening was independently associated with severity (odds ratio 7.1, 95% confidence interval: 3.9-12.9, P < 0.0001). This description of the clinical spectrum of pediatric TB in a low-burden setting demonstrates that adolescents are the group most at risk of experiencing severe TB.

Cost-effectiveness analysis of colorectal cancer screening in a low incidence country: The case of Saudi Arabia.

Background:Colorectal cancer (CRC) screening is cost-effective in many Western countries, and many have successfully implemented CRC screening programs. For countries with a lower CRC incidence, like Saudi Arabia, the value of CRC screening is less evident and requires careful weighing of harms, benefits, and costs.Methods:We used the MISCAN-Colon microsimulation model to simulate a male and female cohort with life expectancy and CRC risk as observed in Saudi Arabia. For both cohorts, we evaluated strategies without screening, with annual or biennial faecal immunochemical testing (FIT), and with 10-yearly or once-only colonoscopy. We also considered different start and end ages of screening. For both cohorts, we estimated lifetime costs and effects of each strategy. We then identified a set of potentially cost-effective strategies using incremental cost-effectiveness ratios (ICERs) defined as the additional cost per additional quality-adjusted life year (QALY).Results:Without CRC screening, an estimated 14 per 1,000 males would develop CRC during their lifetime and 9 would die from CRC. Several strategies proved potentially cost-effective including biennial FIT at ages 55-65 (ICER of $7,400), once-only colonoscopy at age 55 (ICER of $7,700), and 10-yearly colonoscopy at ages 50–65, 45–65, and 45–75 (ICERs of $34,000, 71,000, and 375,000, respectively). For females, risk of CRC was lower and CRC screening was therefore less cost-effective, but efficient strategies were largely similar.Conclusions:Despite low CRC incidence in Saudi Arabia, some FIT or colonoscopy screening strategies may meet reasonable thresholds of cost-effectiveness. The optimal strategy will depend on multiple factors including the willingness to pay per QALY, the colonoscopy capacity, and the accepted budget impact.

Tuberculosis in the paediatric age group: a reflection on transmission

IntroductionPaediatric tuberculosis (TB) disease continues to be a challenge. Difficulties in its diagnosis and limited experience on its treatment in children are some of the reasons to consider the need for specialized paediatric TB centres and to prioritize children in tuberculosis control programmes, particularly in low-incidence countries. We describe the paediatric tuberculosis cases managed in a specialized paediatric outpatient TB centre. Patients and MethodsWe conducted a retrospective analysis of epidemiological and clinical data on TB cases in patients aged less than 18 years in the period ranging from January 2007 to June 2017. ResultsWe identified 46 cases of TB. The median age of the patients was 5 years (IQR, 1.75−13.25). Thirty cases (65.2%) were identified through screening following exposure to TB. Thirty-six children (78%) presented with a median duration of symptoms during 2 weeks, the most frequent being cough (54%) and fever (48%). The findings of the chest radiograph were abnormal in 73.9% of patients, and a CT scan was performed in 82.2%, the findings of which contributed significantly to the decision to treat in 85.3%. Despite collection of different microbiological specimens, diagnostic confirmation was possible in only 12 cases (26.1%). The results of culture and/or nucleic acid amplification tests were positive in 33.3% of samples of sputum, 28.1% of bronchoalveolar lavage and 12.9% of gastric aspirates. The most frequent diagnosis was pulmonary TB (n=31), followed by pleuropulmonary TB (n=6), lymph node disease (n=3), uveitis (n=2), bone tuberculosis, disseminated TB, cerebellar tuberculoma and erythema nodosum (each n=1). ConclusionsTuberculosis in children is an epidemiological indicator of recent transmission of Mycobacterium tuberculosis in the community. Efforts must be made to collect microbiological specimens before initiating treatment whenever possible. Management by an experienced paediatrics team allows an accurate diagnosis even when microbiologic confirmation is not possible.

Recent Advances in Effective Management of Patients with Multidrug-ResistantTuberculosis (MDR-TB)

Tuberculosis (TB) is a major infectious disease worldwide. Most active TB disease cases in humans are caused by Mycobacterium tuberculosis [1]. Some cases in Africa are caused by Mycobacterium africanum while Mycobacterium bovis (bovine bacillus) can also cause TB in individuals who consume unpasteurized milk [1,2]. The global burden of TB is still enormous. According to the World Health Organization (WHO), an estimated 10 million new active TB diseases cases and 1.451 million deaths occurred in 2018, making TB as one of the top 10 killers and the leading cause of death from a single infectious agent [3]. Near 87% of TB cases occurred in 30 high TB burden countries and two-third of all cases in only eight (India, China, Indonesia, Philippines, Pakistan, Nigeria, Bangladesh and South Africa) countries [3]. Most active TB disease cases in high TB burden countries occur as a result of recent infection/reinfection while in low TB incidence countries, they usually arise as a result of reactivation of latent infection, acquired few to several years earlier [2,4,5].

Is it or is it not? Lessons learned from a case of suspected vaccine-associated measles

Background: Measles is a highly infectious viral disease that can cause serious illness and complications. Despite Australia's measles elimination status declared in 2014, the risk of acquiring measles through importation by overseas travellers who are non-immune remains. Identifying wild-type measles in a female who was recently vaccinated with measles mumps rubella (MMR) is a challenge one metropolitan Public Health Unit (PHU) experienced. Case Description: In 2018, a metropolitan Sydney PHU was notified of a positive polymerase chain reaction (PCR) result for measles on a nasopharyngeal swab for a 32 y old female who had recently received an MMR-II vaccination seven days prior to developing symptoms of measles. The case had no known epidemiological link, no recent overseas travel and no contact with recent measles cases during her incubation period. The reference laboratory ran sequencing on the clinical specimen to distinguish between wild-strain and vaccine-type measles. The results of this were inconclusive, however given the recent vaccination and inconsistent clinical symptoms and no identified epidemiological link, a decision was made to re-run the genotyping, collect additional specimens for testing, and quarantine the case until a definitive result was obtained. Subsequently, sequencing and genotyping test results revealed that this indeed was a wild-type measles strain, genotype D8. Discussion: A change in the epidemiology of measles, especially in low incidence countries like Australia, means distinguishing between wild type and vaccine–associated measles has become a new challenge, but critical in implementing a timely public health response. The initial decision to classify this case as vaccine-associated measles was based on the clinical context, epidemiological risk and inconclusive sequencing results. The lack of an epidemiological link created confusion for public health staff when investigating this case. Conclusion: This case investigation and response has demonstrated the challenge for public health with non-typical presentations of wild-type measles, particularly in people who have received one MMR. The reflection of the public health management of this case has provided an opportunity to learn from this experience and can become a valuable teaching tool for public health professionals globally, particularly in low incidence measles countries.

Methylated DNA Markers of Esophageal Squamous Cancer and Dysplasia: An International Study.

Discovery of methylated DNA markers (MDM) of esophageal squamous cell carcinoma (ESCC) has sparked interest in assessing these markers in tissue. We evaluated MDMs in ESCC from three geographically and ethnically distinct populations, and explored the feasibility of assaying MDMs from DNA obtained by swallowed balloon devices. MDMs were assayed in ESCC and normal tissues obtained from the populations of United States, Iran, and China, and from exfoliative cytology specimens obtained by balloons in a Chinese population. Areas under the receiver operating curve (AUC) of MDMs discriminating ESCC from normal tissues were calculated. Random forest prediction models were built, trained on U.S. cases and controls, and calibrated to U.S.-only controls (model 1) and three-country controls (model 2). Statistical tests were used to assess the relationship between dysplasia and MDM levels in balloons. Extracted DNA from 333 ESCC and 322 normal tissues was analyzed, in addition to archival DNA from 98 balloons. For ESCC, model 1 validated in Iranian and Chinese tissues with AUCs of 0.90 and 0.87, and model 2 yielded AUCs of 0.99, 0.96, and 0.94 in tissues from the United States, Iran, and China, respectively. In Chinese balloons, MDMs showed a statistically significant trend of increasing levels with increasing grades of dysplasia (P < 0.004). MDMs accurately discriminate ESCC from normal esophagus in tissues obtained from high- and low-incidence countries. Preliminary data suggest that levels of MDMs assayed in DNA from swallowed balloon devices increase with dysplasia grade. Larger studies are needed to validate these results. MDMs coupled with minimally invasive collection methods have the potential for worldwide application in ESCC screening.

Tuberculous Arthritis in the Ankle in an Immunocompetent Patient: a Case Report

Osteoarticular tuberculosis comprises 1–3% of tuberculosis (TB) patients. In 50% of cases of osteoarticular TB affects the spine. Other joints, such as the ankle, hip, and knee, are less affected. The diagnosis may be delayed for months due to an indolent course and absence of specific signs. Here we report the case of a 42-year-old immigrant immunocompetent male with tuberculosis osteoarthritis of the ankle. The patient experienced intermittent arthritis episodes affecting the left ankle following a fracture of the calcaneus 4 years prior. Initial therapy with anti-inflammatory drugs and empirical antibiotics did not produce improvement. A histological study following a surgical biopsy of the bone provided the diagnosis of tuberculosis. The patient had no respiratory symptomatology, and the chest X-ray was normal. The patient improves his symptoms by administering antitubercular chemotherapy with isoniazid, rifampicin, pyrazinamide, and ethambutol. The diagnosis of osteoarticular TB requires a high index of suspicion, mainly in immunocompetent patients and in low-incidence countries.

Risk of latent and active tuberculosis infection in travellers: a systematic review and meta-analysis.

Achieving tuberculosis (TB) elimination in low TB incidence countries requires identification and treatment of individuals at risk for latent TB infection (LTBI). Persons travelling to high TB incidence countries are potentially at risk for TB exposure. This systematic review and meta-analysis estimates incident LTBI and active TB among individuals travelling from low to higher TB incidence countries. Five electronic databases were searched from inception to 18 February 2020. We identified incident LTBI and active TB among individuals travelling from low (<10 cases/100 000 population) to intermediate (10-100/100 000) or high (>100/100 000) TB incidence countries. We conducted a meta-analysis and meta-regression using a random effects model of log-transformed proportions (cumulative incidence). Subgroup analyses investigated the impact of travel duration, travel purpose and TB incidence in the destination country. Our search identified 799 studies, 120 underwent full-text review, and 10 studies were included. These studies included 1 154 673 travellers observed between 1994 and 2013, comprising 443 health care workers (HCW), 1 068 636 military personnel and 85 594 general travellers/volunteers. We did not identify any studies that estimated incidence of LTBI or active TB among people travelling to visit friends and relatives (VFRs). The overall cumulative incidence of LTBI was 2.3%, with considerable heterogeneity. Among individuals travelling for a mean/median of up to 6months, HCWs had the highest cumulative incidence of LTBI (4.3%), whereas the risk was lower for military (2.5%) and general travellers/volunteers (1.6%). Meta-regression did not identify a difference in incident LTBI based on travel duration and TB incidence in the destination country. Five studies reported cases of active TB, with an overall pooled estimate of 120.7 cases per 100 000 travellers. We found that travelling HCWs were at highest risk of developing LTBI. Individual risk activities and travel purpose were most associated with risk of TB infection acquired during travel.

Knowledge, attitudes, beliefs, and stigma related to latent tuberculosis infection: a qualitative study among Eritreans in the Netherlands

BackgroundTailored and culturally appropriate latent tuberculosis (TB) infection screening and treatment programs, including interventions against TB stigma, are needed to reduce TB incidence in low TB incidence countries. However, we lack insights in stigma related to latent TB infection (LTBI) among target groups, such as asylum seekers and refugees. We therefore studied knowledge, attitudes, beliefs, and stigma associated with LTBI among Eritrean asylum seekers and refugees in the Netherlands.MethodsWe used convenience sampling to interview adult Eritrean asylum seekers and refugees: 26 semi-structured group interviews following TB and LTBI related health education and LTBI screening, and 31 semi-structured individual interviews with Eritreans during or after completion of LTBI treatment (November 2016–May 2018). We used a thematic analysis to identify, analyse and report patterns in the data.ResultsDespite TB/LTBI education, misconceptions embedded in cultural beliefs about TB transmission and prevention persisted. Fear of getting infected with TB was the cause of reported enacted (isolation and gossip) and anticipated (concealment of treatment and self-isolation) stigma by participants on LTBI treatment.ConclusionThe inability to differentiate LTBI from TB disease and consequent fear of getting infected by persons with LTBI led to enacted and anticipated stigma comparable to stigma related to TB disease among Eritreans. Additional to continuous culturally sensitive education activities, TB prevention programs should implement evidence-based interventions reducing stigma at all phases in the LTBI screening and treatment cascade.

The seedbeds of Tuberculosis: is it time to target congregate settings and workplaces?

SummaryCountries where the incidence of Tuberculosis (TB) is low display a low transmission rate in the general population, and this rate has progressively declined in recent decades; however, TB epidemiology has shown a shift of the disease burden from the general population to specific populations at higher risk, such as vulnerable individuals and hard-to-reach groups. In low-incidence countries, preventive and therapeutic strategies must therefore be geared towards targeted interventions in these populations, with the priority being to promptly identify and treat latent tuberculosis infection (LTBI) rather than manage infectious cases. One of the most complex challenges in this area is to identify population subgroups with increased incidence/prevalence of LTBI/TB.The aim of this study was to provide a concise overview of the main studies and available evidence concerning the epidemiology of TB and LTBI in non-healthcare congregate settings, with specific emphasis on studies conducted in occupational settings and workplaces.Recognizing settings at increased risk might contribute to eliminating TB in low-incidence countries, a challenge which requires tailored responses.Occupational and preventive medicine has a major role to play in directing ad hoc policies and programs of LTBI surveillance. If TB is to be eradicated, it is essential to contain the seedbeds of infection: indeed, as long as a large reservoir of infected subjects exists, new active TB cases may arise at any time.